Revolutionizing HIV Prevention and Treatment: The Role of Biospecimens in Long-Acting Therapy Development

February 3, 2026

The landscape of HIV prevention and treatment is undergoing a transformative shift. Long-acting injectable therapies promise to overcome adherence challenges, reduce pill burden, and improve quality of life for millions of people living with or at risk for HIV. From long-acting pre-exposure prophylaxis (PrEP) to extended-release antiretroviral treatment, these innovations are among the most significant advances in HIV care since combination antiretroviral therapy (ART) arrived in the 1990s.1,2

Developing, validating, and optimizing these therapies relies fundamentally on access to well-characterized biospecimens from patients with confirmed HIV infection across diverse populations and treatment experiences. From study design to receipt of samples, researchers need specimens paired with comprehensive clinical annotation — viral load, CD4/CD8 counts, treatment history, resistance profiles, and longitudinal outcomes. These resources let investigators understand drug pharmacokinetics, assess immune recovery, identify biomarkers of response, and advance cure strategies.3

Access to HIV biospecimens from treatment-naïve and treatment-experienced individuals, including those on specific long-acting regimens, provides invaluable resources for accelerating the next generation of HIV therapeutics and prevention.

The Evolution of HIV Therapy: From Daily Pills to Long-Acting Injectables

The journey from the early days of HIV therapy — dozens of pills daily with severe side effects — to today’s streamlined regimens is one of medicine’s great success stories. Modern single-tablet regimens have dramatically improved adherence and outcomes, transforming HIV from a fatal diagnosis into a manageable chronic condition for many patients.4

However, daily oral therapy still presents challenges:

Adherence Requirements: Missing even occasional doses can lead to viral rebound and drug resistance. Studies consistently show that perfect or near-perfect adherence is required for optimal viral suppression.5

Stigma and Privacy Concerns: Daily pill-taking can be a constant reminder of HIV status and may compromise privacy in shared living situations, adding psychological burden and disclosure concerns.

Access Barriers: Challenges with prescription refills, pharmacy access, insurance coverage, and healthcare navigation can interrupt treatment continuity.

PrEP Uptake Limitations: Despite proven efficacy, uptake of daily oral PrEP remains suboptimal in many at-risk populations, partly due to adherence concerns and stigma.6

Long-acting injectable therapies address many of these challenges, reducing administration frequency from 365 doses per year to as few as 6-12 doses annually, given by healthcare providers in clinical settings.

Geographic Distribution of Long-Acting HIV Therapy Access Across the United States

The rollout of long-acting injectable HIV therapies has expanded access across diverse regions, though implementation varies by location. Understanding regional availability supports equitable access and informs biospecimen collection strategies:

Major US Regions with Long-Acting Therapy Centers

  1. Northeast Region – New York, Massachusetts, Pennsylvania, New Jersey, Connecticut, and Maryland host major academic medical centers offering long-acting PrEP and treatment options, with high-volume HIV clinics in urban areas like New York City, Boston, and Philadelphia serving diverse patient populations.
  2. Southeast Region – Florida, Georgia, North Carolina, South Carolina, Tennessee, and Louisiana have expanded long-acting therapy access through public health initiatives targeting regions with elevated HIV incidence, particularly in Atlanta, Miami, Charlotte, and New Orleans.
  3. Midwest Region – Illinois, Ohio, Michigan, Wisconsin, Minnesota, and Missouri provide long-acting injectable therapies through university hospitals and community health centers in Chicago, Cleveland, Detroit, and Minneapolis, addressing both urban and rural access gaps.
  4. Southwest Region – Texas, Arizona, and New Mexico offer long-acting HIV prevention and treatment through specialized infectious disease clinics in Houston, Dallas, San Antonio, Phoenix, and Albuquerque, serving border communities and diverse populations.
  5. West Coast Region – California, Washington, and Oregon lead in long-acting therapy adoption with extensive implementation in San Francisco, Los Angeles, San Diego, Seattle, and Portland, supported by strong public health infrastructure and research institutions.
  6. Mountain West Region – Colorado, Utah, and Nevada have established long-acting injection capabilities in Denver, Salt Lake City, and Las Vegas, expanding access in traditionally underserved mountain and desert communities.

This geographic diversity creates opportunities for multi-regional biospecimen collection studies that capture varied patient demographics, treatment patterns, and outcomes across the United States.

Long-Acting PrEP: Transforming HIV Prevention

The approval and rollout of long-acting cabotegravir for HIV prevention marked a watershed moment. Clinical trials demonstrated superior efficacy versus daily oral PrEP, with 66-89% greater protection against HIV acquisition in at-risk populations.7,8 Administered as an injection every two months, long-acting cabotegravir eliminates daily adherence requirements while maintaining high protective efficacy.

Recent data presented at IDWeek 2024 showcased promising results for next-generation long-acting PrEP combinations, including weekly oral islatravir plus lenacapavir. These regimens offer potential for even longer dosing intervals — quarterly or even twice-yearly — further reducing treatment burden and improving accessibility.9

Research Priorities in Long-Acting PrEP

Pharmacokinetics and Drug Levels

Understanding drug concentrations in blood, genital tissues, and rectal tissues over extended dosing intervals requires serial specimen collections from PrEP users. Human plasma with timed collections relative to injection dates enables pharmacokinetic modeling, while tissue biopsies assess drug penetration to sites of potential HIV exposure. Human serum specimens provide complementary data for antibody responses and drug protein binding studies.

Immune Activation and Biomarkers

Characterizing baseline immune status and potential biomarkers predicting PrEP efficacy or breakthrough infection risk remains an active area. Human PBMCs enable immune phenotyping and identification of host factors influencing prevention success, while human CD3+ T cells allow focused investigation of T-cell activation markers and HIV target cell populations.

Resistance Development

Monitoring for drug resistance in rare breakthrough infections requires immediate access to specimens for viral genotyping and phenotypic resistance testing. Human whole blood collections with rapid processing support surveillance efforts and enable comprehensive viral load monitoring with cellular analysis.

Real-World Effectiveness

Comparing long-acting versus oral PrEP effectiveness in diverse populations requires specimens from implementation science studies paired with detailed behavioral, adherence, and outcomes data.

Long-Acting Treatment for People Living with HIV

For the estimated 1.2 million people living with HIV across the United States, long-acting injectable ART offers an alternative to daily oral regimens. The combination of cabotegravir and rilpivirine, given as monthly or every-two-month injections, has demonstrated non-inferiority to daily oral ART in maintaining viral suppression.10

Advantages of Long-Acting ART

  • Eliminates daily pill-taking and associated stigma
  • Provides reassurance through healthcare provider-administered dosing
  • Reduces gastrointestinal side effects common with oral medications
  • Achieves predictable drug levels without adherence variability
  • May improve quality of life and treatment satisfaction

Research using biospecimens from patients on long-acting ART investigates:

Viral Reservoir Dynamics: Long-acting ART may differentially impact HIV reservoirs in blood and tissues compared with oral regimens. Access to longitudinal human PBMC collections enables tracking of reservoir size and distribution over time, informing cure strategies. High-quality human leukopaks provide abundant peripheral blood mononuclear cells for comprehensive reservoir studies, including HIV DNA quantification and viral outgrowth assays.

Immune Reconstitution: Characterizing CD4 recovery, immune activation markers, and inflammatory profiles during long-acting versus oral ART provides insights into immunologic benefits beyond viral suppression. Comprehensive immune profiling requires matched plasma and cellular specimens with detailed immunophenotyping.

Treatment Durability: Long-term viral suppression rates, emergence of resistance, and durability of response require longitudinal specimen collections paired with viral load measurements and genomic annotation including resistance mutations.

Patient-Reported Outcomes: Correlating biological markers with quality of life, treatment satisfaction, and adherence patterns requires integration of biospecimen data with validated patient-reported outcome measures.

Biospecimen Requirements for Long-Acting HIV Therapy Research

The unique characteristics of long-acting therapies create specific biospecimen requirements:

Longitudinal Collections with Extended Follow-Up

Unlike daily oral therapy studies, long-acting therapy research requires specimen collections spanning months to years, with strategic timepoints aligned to dosing schedules. Serial collections enable assessment of:

  • Drug washout kinetics after final injection
  • Viral rebound patterns if treatment is interrupted
  • Long-term immune system recovery
  • Natural history of HIV on extended regimens

Human leukopak collections provide optimal cell yields for time-course studies requiring extensive cellular analyses, while bulk plasma specimens support large-scale pharmacokinetic and biomarker validation studies.

Comprehensive Treatment History Documentation

Specimens must be accompanied by detailed records of:

  • Previous antiretroviral regimen history
  • Reasons for switching to long-acting therapy
  • Injection dates and locations (deltoid vs. gluteal)
  • Any missed or delayed injections
  • Concurrent medications

Viral Load and Resistance Data

High-quality viral load measurements at regular intervals, coupled with resistance genotyping when viral rebound occurs, provide essential context for biospecimen interpretation. Pre-existing resistance mutations may predict long-acting therapy outcomes.

Demographic and Clinical Covariates

Understanding whether long-acting therapy outcomes differ across populations requires diverse cohorts with comprehensive annotation of:

  • Age, sex, race/ethnicity
  • HIV transmission category
  • Time since HIV diagnosis
  • Baseline CD4/CD8 counts
  • Co-morbidities and co-infections (HBV, HCV, CMV)

Regional HIV Biospecimen Collection Networks Supporting Long-Acting Therapy Research

Strategic biospecimen collection from diverse geographic regions ensures research findings apply to the full spectrum of US populations affected by HIV:

State-by-State Biospecimen Collection Capabilities

  1. California – Los Angeles, San Francisco, San Diego, and Sacramento collection sites provide access to diverse urban populations, including large LGBTQ+ communities, Hispanic/Latino populations, and Asian/Pacific Islander groups with varied HIV prevalence and treatment patterns.
  2. New York – New York City, Albany, Rochester, and Buffalo collection networks capture specimens from high-incidence areas with significant representation of African American, Hispanic/Latino, and immigrant populations receiving long-acting therapies.
  3. Florida – Miami, Fort Lauderdale, Orlando, Tampa, and Jacksonville collection centers serve populations with high HIV burden, including substantial Caribbean and Latin American immigrant communities and aging populations living long-term with HIV.
  4. Texas – Houston, Dallas, San Antonio, Austin, and El Paso collection sites enable specimen procurement from border regions, large metropolitan areas, and diverse racial/ethnic populations including significant Hispanic/Latino representation.
  5. Georgia – Atlanta metropolitan area collection capabilities support research in the Deep South, addressing health disparities and accessing African American populations disproportionately affected by HIV.
  6. Illinois – Chicago and surrounding areas provide specimens from Midwest urban populations, including significant representation of African American and Hispanic/Latino communities with unique treatment access patterns.
  7. Pennsylvania – Philadelphia and Pittsburgh collection infrastructure supports research in Northeastern populations, including urban areas with ongoing opioid epidemic impact on HIV transmission.
  8. North Carolina – Raleigh, Durham, Charlotte, and Greensboro collection sites capture specimens from growing Southern metropolitan areas with mixed urban-rural populations and emerging HIV hotspots.
  9. Arizona – Phoenix and Tucson collection centers enable specimen procurement from Southwestern populations, including Native American communities and US-Mexico border regions with distinct epidemiological patterns.
  10. Washington – Seattle and Spokane collection capabilities support Pacific Northwest research, accessing populations with high PrEP uptake and progressive HIV care models influencing long-acting therapy adoption.

This geographically distributed collection network ensures biospecimen resources represent the demographic, socioeconomic, and regional diversity of people living with or at risk for HIV across all US regions.

Advancing HIV Cure Research with Biospecimens

While long-acting therapies represent significant treatment advances, the ultimate goal remains HIV cure or long-term remission without ongoing therapy. Biospecimens from individuals on long-acting regimens provide unique opportunities to study:

Reservoir Persistence: Investigating whether long-acting therapies differentially impact HIV reservoirs compared with oral ART. Studies require PBMCs, rectal tissue, lymph node tissue, and cerebrospinal fluid when available to comprehensively assess reservoir distribution.11 GMP-grade leukopaks provide clinical-grade cell products for cell therapy and gene therapy cure strategies, meeting stringent regulatory requirements for translational research.

Immune Responses: Characterizing HIV-specific T-cell and antibody responses during prolonged viral suppression. Flow cytometry panels assessing T-cell exhaustion markers, memory phenotypes, and functional capacity require viable human PBMCs with documented cryopreservation and thaw viability. Isolated human CD3+ T cells enable enriched analysis of HIV-specific cellular immune responses without interference from other cell populations.

Biomarkers of HIV Persistence: Identifying markers that correlate with reservoir size and predict likelihood of viral rebound after treatment interruption. Candidate biomarkers include HIV DNA in PBMCs, cell-associated HIV RNA, and inflammatory markers such as sCD163, sCD14, and IL-6 measured in plasma specimens.12

Latency Reversal Strategies: Testing interventions designed to “shock and kill” latent HIV requires baseline specimens before intervention and serial post-intervention collections to assess viral reactivation and immune-mediated clearance.

Access to specimens from patients enrolled in analytical treatment interruption studies — where ART is carefully stopped to assess viral rebound kinetics — provides invaluable data for cure research, though such studies require intensive monitoring and immediate access to specimen collection capabilities.

Supporting Innovation: Custom HIV Biospecimen Collections

Organizations like SanguineBio support HIV research through comprehensive infectious disease biospecimen collections and prospective collection services tailored to study requirements. Custom HIV cohorts can be designed to match:

  • Specific antiretroviral regimens (including long-acting therapies)
  • Treatment status (naïve, experienced, or virologically suppressed)
  • Viral load ranges and CD4 count criteria
  • Co-infection profiles
  • Demographic characteristics
  • Geographic distribution across the United States

From study design to receipt of samples, streamlined processes enable rapid cohort assembly while maintaining quality standards for downstream applications including viral load quantification, HIV DNA/RNA measurement, immune phenotyping, and multi-omics analyses.

The Future of HIV Therapy: Ultra-Long-Acting Regimens and Beyond

The HIV therapeutics pipeline continues to evolve toward even longer-acting formulations. Investigational agents target dosing intervals of 6 months or longer, with some studies exploring annual dosing for both prevention and treatment.13 These ultra-long-acting approaches may use:

  • Novel drug delivery systems (implants, microarray patches)
  • Broadly neutralizing antibodies with extended half-lives
  • Long-acting formulations of new drug classes
  • Combination products optimized for minimal dosing frequency

Each advancement requires robust biospecimen resources to:

  • Establish proof-of-concept in early studies
  • Demonstrate safety and efficacy in clinical trials
  • Monitor real-world effectiveness after approval
  • Identify and characterize rare adverse events or resistance patterns

The lessons learned from current long-acting therapies will inform design of next-generation studies, with biospecimen collection strategies optimized for extended follow-up and comprehensive biological monitoring.

Conclusion

Long-acting injectable HIV therapies represent a paradigm shift in prevention and treatment, with potential to dramatically improve outcomes, increase treatment uptake, and advance progress toward ending the HIV epidemic. Developing and optimizing these interventions depends critically on access to well-characterized biospecimens from diverse patient populations.

Infectious disease biospecimen collections with comprehensive clinical annotation enable researchers to understand pharmacology, predict treatment outcomes, identify biomarkers, and advance cure strategies. As the field moves toward ultra-long-acting regimens and novel combination approaches, investment in longitudinal biospecimen resources with geographic diversity will remain essential to translating scientific innovation into real-world impact for people living with and at risk for HIV across all regions of the United States.

Explore our comprehensive portfolio of human PBMCs, plasma, leukopaks, and other HIV biospecimens, or contact our team to discuss custom collection services for your HIV research program. Learn more about our infectious disease biospecimen collection.

References

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  7. Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women. N Engl J Med. 2021;385(7):595-608. doi:10.1056/NEJMoa2101016
  8. Delany-Moretlwe S, Hughes JP, Bock P, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 2022;399(10337):1779-1789. doi:10.1016/S0140-6736(22)00538-4
  9. New Data to be Presented at IDWeek 2024 Reinforce Merck’s Broad and Diverse Vaccines and Infectious Disease Pipeline and Portfolio. Published 2024. Accessed December 9, 2024. https://www.merck.com/news/new-data-to-be-presented-at-idweek-2024-reinforce-mercks-broad-and-diverse-vaccines-and-infectious-disease-pipeline-and-portfolio/
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  12. Kelesidis T, Kendall MA, Yang OO, Hodis HN, Currier JS. Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection. J Infect Dis. 2012;206(10):1558-1567. doi:10.1093/infdis/jis545
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